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M Knoke

Publications and source records attributed to M Knoke.

At least 19 recordsLinked to original sources

Funguria and Candida-specific immunoglobulins in patients with systemic candidosis.

UNLABELLED: Funguria, indirect anti-Candida haemagglutination test (C-IHT) and Candida-specific immunoglobulins C-IgM, C-IgG and C-IgA were investigated under suspicion of systemic candidosis in critically ill patients. A total of 143 urine cultures were studied for Candida from 74 adults and a median count of log 3.0 CFU ml-1 was found. Most isolated Candida species were Candida albicans and Candida glabrata. In 14 cases of candidaemia there was no regular agreement between the finding of Candida species in blood and urine. In cases with candiduria > = or log 3.0 CFU ml-1 a stronger increase of C-IHT titres and all three Candida-specific immunoglobulins after 5-7 days was observed. Some statistically significant correlations were found between the levels of urinary yeast counts and immunological parameters concerning C-IHT, C-IgA and C-IgG on the first day and after 5-7 days. Clinical findings in some cases coincided well with funguria and courses of titres before and after treatment. CONCLUSION: In critically ill patients suspected of having systemic candidosis not only blood cultures should be made. Cultural studies with specimens taken from different sites including funguria are essential for a complete specific serological investigation.

Aged↗

Induction of P-glycoprotein by rifampin increases intestinal secretion of talinolol in human beings: a new type of drug/drug interaction.

BACKGROUND: P-Glycoprotein is an efflux pump in many epithelial cells with excretory function. It has been demonstrated that rifampin (INN, rifampicin) induces P-glycoprotein, particularly in the gut wall. We therefore hypothesized that rifampin affects pharmacokinetics of the P-glycoprotein substrate talinolol, a beta1-blocker without appreciable metabolic disposition but intense intestinal secretion in human beings. METHODS: Pharmacokinetics of talinolol (a single dose of 30 mg administered intravenously or 100 mg administered orally for 7 days) and duodenal expression of the MDR1 gene product P-glycoprotein as assessed by reverse transcriptase-polymerase chain reaction of the MDR1-messenger ribonucleic acid, by immunohistochemistry and Western blot analysis were analyzed before and after coadministration of rifampin (600 mg per day for 9 days) in 8 male healthy volunteers (age 22 to 26 years). RESULTS: During rifampin treatment, the areas under the curve of intravenous and oral talinolol were significantly lower (21% and 35%; P < .05). Treatment with rifampin resulted in a significantly increased expression of duodenal P-glycoprotein content 4.2-fold (2.9, 6.51) (Western blot) and messenger RNA was increased in six of the eight volunteers. P-Glycoprotein expression in biopsy specimens of gut mucosa correlated significantly with the systemic clearance of intravenous talinolol (rs = 0.74; P < .001). CONCLUSIONS: Rifampin induces P-glycoprotein-mediated excretion of talinolol predominantly in the gut wall. Moreover, clearance of talinolol from the blood into the lumen of the gastrointestinal tract may be predicted by the individual intestinal P-glycoprotein expression. Thus we describe a new type of steady-state drug interaction affecting compounds that are subject to transport rather than metabolism.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Oesophageal candidosis in intensive care patients.

We conducted upper intestinoscopies in 124 intensive care patients, six of whom had oesophageal candidosis. Of these, two also had Candida plaque in the stomach. The patients at the intensive care unit (ICU) had a mean Apache-II score of 26.7; whereas the score was 29.5 in patients with Candida oesophagitis. A significant increase of Candida antibodies was found in 59 of 124 patients (47.6%), including all patients with oesophageal candidosis. Presumably, mycotic infections of other sites were present. The severity by which mucous membranes were affected correlated well with microscopically evident invasiveness.

Candida↗

Fungal resistance.

Fungal resistance is caused by an acquisition of intrinsically resistant species, by selection of resistant strains from a population or by mutation of an initially susceptible strain. According to different classes of antimycotics there are different resistance mechanisms: differences in the uptake mechanisms, drug target alterations, mostly the ergosterol-biosynthesis pathway, and the efflux or pumping mechanisms to the outside.

Animals↗

[Gastrointestinal microecology of humans and Candida].

Microecology looks for the relationships between microorganisms and their natural environment in definite sites and their physiological and pathological effects. From birth Candida spp. are often but not always detectable in the human gastrointestinal tract. In cases of reduced defense the tract may be a source of infection to the macroorganism. In healthy subjects the incidence of Candida is between 23% and 76% in quantities between 10(2)-10(4) CFU/ml or g dependent on site. Evidence is most frequent in oral cavity and faeces. Tolerance for Candida spp. is different in the stomach and duodenum due to differences in acidity. Changes in the occurrence of Candida spp. are possible depending on age, different diseases and exogenous influences as nutrition, stress and drugs. In an endocrine stress model we found no yeasts in the duodenal juices of 7 subjects before and after stress situation, but a clear decrease of yeasts in the faeces. The formation of metabolic products by Candida is secondary to the whole of microbial fermentation in the human orointestinal tract. Colonizing strains of C. albicans are normally present in small or moderate numbers and only they are regarded as part of the resident gastrointestinal microflora.

Candida↗

The continuous flow culture as an in vitro model in experimental mycology.

We used the model of continuous flow culture (cfc) to study the growth of Candida species. This model allows special test conditions: a long generation time of 15-20 hs, controlled limitation of nitrogen sources and carbohydrates, comparison of the growth under aerobic and anaerobic conditions simultaneously. These conditions were used to study the effect of antimycotic drugs, mainly during a long time of 7 to 10 days. Germ tube formation as a virulence factor was more abundant and faster in cfc of strains with a stronger adherence to buccal epithelium cells. Co-cultivation of C. albicans and C. glabrata allowed conclusions for their colonization in vivo. A biofilm on the glass wall of the culture vessel led to mycelium formation by C. albicans. Concomitantly the growth of C. glabrata was favoured. Growth of C. albicans in the gastrointestinal flora was reduced by masses of bacteria and their multiple metabolic activities. A remarkable growth of C. albicans was only to be seen if the ecosystem was destroyed e.g. by antibacterial antibiotics. The influence of fluconazole in a long-term follow up study under anaerobic conditions showed an inhibition of C. albicans in 99.9%. This means fungicidal efficacy.

Candida↗

Influence of ciprofloxacin and other antimicrobial drugs on different Escherichia coli strains in continuous-flow cultures under aerobic and anaerobic conditions.

In continuous-flow culture, long generation times and high bacterial counts favour survival of bacteria. A chemotherapeutic agent that achieves a bactericidal effect under these circumstances can therefore be seen as highly effective. In our continuous-flow culture we obtained bactericidal effects with ciprofloxacin 1-2 mg/L, cefotaxime 4 mg/L and mezlocillin 32 mg/L. These effects were seen irrespective of whether conditions were aerobic or anaerobic. There were no significant differences between monocultures and mixed cultures simulating faecal flora with the various Escherichia coli strains tested. Cefotaxime had an initial effect but an increase in counts was then observed as a result of regrowth of E. coli survivor strains in aerobic monoculture and mixed cultures. Mezlocillin was completely bactericidal in monocultures, but regrowth occurred in mixed cultures under anaerobic conditions. Neither the bacterial composition of this culture nor the resistance pattern explained this regrowth. These results were observed in long-term experiments followed for up to 7 days. We conclude that the antibiotics tested are highly effective against E. coli under unfavourable conditions simulating in-vivo situations.

Aerobiosis↗

[Fungi in the oro-intestinal tract and their scientifically founded status].

The orointestinal tract is a reservoir for facultatively pathogenic fungi, especially Candida albicans. In all of its sections in immunocompromised hosts, the occurrence of a mucosal mycosis is possible which may be the starting point of an infection of internal organs. The mouth and esophagus are the most often affected locations. A synopsis of clinical (including endoscopic) findings, mycological cultivation and mycoserology is important in diagnostics. There is no connection between the incidence of Candida in the orointestinal tract and multiple local symptoms like fatigue, headache, heartburn and others called "candidiasis hypersensitivity syndrome" or "mycophobia".

Candida↗

Mycological aspects of gastrointestinal microflora.

There are two aspects about the presence of Candida in the human orointestinal tract: (i) it is a part of normal human flora and (ii) it is a risk factor for immunocompromised patients. The orointestinal tract can be considered a reservoir for Candida species, several of which are from the oral cavity, stomach, duodenal juice and faeces. Their germ counts in normal small and large bowel do not exceed 10(4) cfu/ml resp.g. The input of Candida to a well-developed faecal flora system under continuous flow culture conditions did not lead to a multiplication of the yeast. The take in of faecal flora into a Candida continuous flow culture diminish Candida germ counts. If, however, the faecal flora was destroyed, e.g. by antibiotics, we found the yeasts multiplying, with the formation of germ tubes and mycelial structures. Colonization by Candida has to be seen as a starting-point of the development of subsequent candidosis in immunosuppressed or intensive care patients. The best protection against Candida colonization in the gut is the existence of a normal bacterial flora. Lactulose, which promotes the Gram-positive potential of faecal flora, may protect indirectly by supporting the indigenous flora.

Adult↗

Dynamics of Candida isolations from humans from 1992-1995 in Greifswald, Germany.

In the period 1992-95 there was a significant shift in the spectrum of Candida species in the University Hospital in Greifswald. During this time, the annual number of specimens taken for mycological investigations of adults increased threefold (total n = 11,568). The isolation rate of Candida species was 50.5%. The percentage of C. albicans isolates decreased from 76% to 54.4% with the lowest level in 1994. The opposite trend in the occurrence of non-C. albicans species was seen, for example the occurrence of C. glabrata, from 11.7% to 28.4%. We found only 98 strains of C. parapsilosis (1.4%) during the 4 years. The occurrence of Candida species in a variety of habitats was different. During the 4 years, the same annual percentages of C. albicans (mean 87.9%) were isolated from endoscopic oesophageal smears, whereas the distribution of Candida yeasts from the oral cavity, the respiratory tract, faeces and urine had changed. Over the years, at these locations, C. albicans was less frequently isolated and non-C. albicans species clearly increased. The highest occurrence of C. glabrata was found in urine, in which the isolation percentage almost doubled from 23.1% to 40.9% in 1994. In contrast to adults, in all specimens originating from a paediatric clinic that included neonatology the occurrence of C. albicans was high (83.5% in 1995), but the isolation rate of Candida species was low (12.3%). These results are important because of the differences in yeast susceptibility, of non-C. albicans species in particular, against antifungal drugs.

Adult↗

[Clinical pictures of orointestinal candidiasis. Fiction or reality?].

The oral cavity and the oesophagus are the main sites of involvement in orointestinal candidosis. The clinical pictures of these manifestations are characterized. Involvement of the stomach as well as the small and large intestine is an exceedingly rare but possible manifestation. There are obviously no repeatedly occurring characteristical symptoms, neither have controlled studies confirmed such characteristics. Recently a discussion has arised-undoubtedly to a large extent influenced by public media-to explain a variety of in particular gastrointestinal symptoms as a consequence of an apparent "mycotic infection of the orointestinal tract" as "a new mass disease". These reports lack any scientific basis supported by experimental or clinical studies. There are similarities to the "candidiasis hypersensitivity syndrome" or "the yeast connection", the existence of which has been critically denied by experts. Corresponding references are given. The author realizes the necessity to oppose this public debate on a critical scientific basis and to answer open questions by controlled studies.

Antifungal Agents↗

[Growth of Candida albicans in normal and altered fecal flora in the continuous flow culture model].

We used the model of fecal microflora under continuous flow culture (cfc) conditions to study the growth of Candida albicans in mixed cultures. The development of Candida is usually limited by the high germ counts of aerobic and anaerobic bacteria. Neither by the continuous inflow of C. albicans-cfc-monocultures nor by intermittent input of highly concentrated suspensions of C. albicans into the system a growth in fecal flora could be obtained. If the system was run under aerobic conditions a development of C. albicans with few hyphal growth could be observed. After some days however, the fecal flora again suppressed a further development of the yeasts. Only a marked destruction of the aerobic and anaerobic microflora by antibiotics resulted in a growth or overgrowth of Candida albicans.

Anti-Bacterial Agents↗

[Mycotic complications in patients with chronic liver diseases and pancreatitis].

UNLABELLED: We studied 15 patients with mostly alcoholic liver diseases and 25 patients with acute or chronic pancreatitis with regard to occurrence of yeasts in different microbiological samples and corresponding serological findings. In about a half of the patients with liver diseases yeast counts and serological titres were already raised in the first mycological investigation. Patients with pancreatitis, however, showed only little or negative cultural and serological results. This changed during the course of disease, where they developed significantly higher yeast counts and serotitres. Finally two case reports are presented: two patients with infected pancreatic pseudocysts (including a case of aspergillosis). CONCLUSIONS: in patients with decompensated chronic liver diseases an early search for mycological complications is recommended. In pancreatic diseases these complications are rather seen later in the course of the disease, especially under intensive care conditions. Therefore, we encourage surveillance cultures and control of serotitres in these patients.

Acute Disease↗

[One hundred years of cryptococcosis. Medical mycology in the 19th century in Greifswald].

Not later than 1842 medico-mycological investigations began at Greifswald in Germany following the appointment of Wilhelm Baum (1799-1883) to the chair of surgery at the university. This is indicated by some theses as well as by the discovery of the contagious characteristics of pityriasis versicolor by Carl Ferdinand Eichstedt (1816-1892) who found a fungus as the cause (1846), which was named Microsporon furfur later (C. Robin 1853). In 1868 the physician (Karl) Friedrich Mosler (1831-1911) published clinical-mycological studies and investigations on animal feeding with yeasts. Some time later (1870) Friedrich Grohé (1830-1886) and his assistants Alwin R. A. Block (1843-?) and M. R. Roth of the Pathological Institute described results of transmission-studies with "Aspergillus glaucus, Penicillium glaucum and yeast". The successor to the chair, Paul Grawitz (1850-1932), also published results of his own mycological investigations. Finally, on 7 July, 1894, during the evening lecture of the Greifswald Medical Society Abraham Buschke (1868-1943) from the Hospital of Surgery gave a talk "on a peculiar disease caused by coccidia" followed by the talk of pathologist Otto Busse (1867-1922) on a "demonstration of a pathogenic coccidia species". Busse's subsequent publications are the first proper descriptions of cryptococcosis (1894 f). Nevertheless, Cryptococcus neoformans has been named in connection with F. Sanfelice, whose results were published later (1895).

Cryptococcosis↗

[Dimorphism of Candida albicans in the model of continuous flow culture].

We investigated the opportunistic pathogen Candida albicans in a continuous flow culture with regard to particular growth conditions. Germ counts of only 10(7) cfu/ml were obtained in a steady state of an anaerobic culture. In a parallel experiment with aerobic conditions excessive growth occurred and the invasive forms of Candida, i.e. germ tubes and pseudomycelium, also developed. Neither by different carbohydrates and concentration of nutrients in the culture medium nor by changing the flow rate the growth of Candida could be influenced. Excessive overgrowth was triggered by a sufficient oxygen supply.

Aerobiosis↗